Structural and Functional Integration of Tissue-Nonspecific Alkaline Phosphatase Within the Alkaline Phosphatase Superfamily: Evolutionary Insights and Functional Implications

Metabolites, Journal Year: 2024, Volume and Issue: 14(12), P. 659 - 659

Published: Nov. 25, 2024

Phosphatases are enzymes that catalyze the hydrolysis of phosphate esters. They play critical roles in diverse biological processes such as extracellular nucleotide homeostasis, transport molecules across membranes, intracellular signaling pathways, or vertebrate mineralization. Among them, tissue-nonspecific alkaline phosphatase (TNAP) is today increasingly studied, due to its ubiquitous expression and ability dephosphorylate a very broad range substrates participate several different functions. For instance, TNAP hydrolyzes inorganic pyrophosphate (PPi) allow skeletal dental Additionally, pyridoxal cellular uptake, stimulate vitamin B6-dependent reactions. Furthermore, has been identified key enzyme non-shivering adaptive thermogenesis, by dephosphorylating phosphocreatine mitochondrial creatine futile cycle. This latter recent discovery others suggest list functions may be much longer than previously thought. In present review, we sought examine within (AP) superfamily, comparing sequence, structure, evolutionary trajectory. The AP characterized conserved central folding motif mixed beta-sheet flanked alpha-helices, includes six subfamilies: AP, arylsulfatases (ARS), ectonucleotide pyrophosphatases/phosphodiesterases (ENPP), phosphoglycerate mutases (PGM), phosphonoacetate hydrolases, phosphopentomutases. Interestingly, ENPP family members appear same metabolic pathways extra-skeletal mineralization vertebrates inhibited ENPP1-mediated ATP into inhibitor PPi, which hydrolyzed expressed skeleton. Better understanding how other differ structurally will useful clarify their complementary Structurally, shares catalytic core with superfamily but unique features affecting substrate specificity activity. review also aims highlight importance oligomerization stability function, role metal ion coordination, particularly magnesium, APs. By exploring structural functional diversity discussing extent exert redundant, complementary, specific functions, this illuminates pressures shaping these physiological roles, offering insights TNAP’s multifunctionality implications for health disease.

Language: Английский

ENPP1/CD203a-targeting heavy-chain antibody reveals cell-specific expression on human immune cells

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 82(1)

Published: Dec. 18, 2024

Language: Английский